Immunomorphological and Ultrastructural Characterization of Langerhans Cells and a Novel, Inflammatory Dendritic Epidermal Cell (IDEC) Population in Lesional Skin of Atopic Eczema

Abstract

We investigated epidermal cell suspensions prepared from lesional and nonlesional atopic eczema skin, other inflammatory skin conditions, and normal human skin for high-affinity IgE receptor (Fc epsilon RI) expression on dendritic CD1a cells by quantitative flow cytometric analysis. A single CD1a bright/CD1b neg/Fc epsilon RI dim/CD23 neg/CD32 dim/HLA-DR bright/CD36 neg population was found in normal skin. In contrast, lesional skin of atopic eczema and other inflammatory skin diseases harbored variable proportions of two distinct CD1a populations. Both populations exhibited typical ultrastructural features of Langerhans cells, but the second one lacked Birbeck granules and was unreactive to the Birbeck granule-specific LAG antibody. Both populations differed phenotypically: classical Langerhans cells were CD1a bright/CD1b neg/Fc epsilon RI dim/CD23 neg/CD32 dim/HLA-DR bright/CD36 dim, while the second population was CD1a dim/CD1b dim/Fc epsilon RI bright/CD23 dim/CD32 dim/HLA-DR bright/CD36 bright. The highest Fc epsilon RI expression was found on the second CD1a population in lesional atopic eczema skin. Furthermore, Fc epsilon RI expression on CD1a cells correlated significantly with the serum IgE level of the patients. Thus, a distinct population of CD1a inflammatory dendritic epidermal cells different from classical Langerhans cells appears in the epidermis of lesional skin and is subjected to specific signals leading to the upregulation of Fc epsilon RI in atopic eczema skin.

Atopic dermatitis: from the genes to skin lesions

“…Quantitative¯ow cytometric examination has demonstrated a signi®cant upregulation of Fc e RI molecules on the CD1a-expressing epidermal dendritic cells isolated from lesional skin in AD (45,46). Beside the Birbeck's granule-containing Langerhans cells, a second CD1a-expressing cell population lacking this Langerhans cell-speci®c ultrastructural hallmark could be demonstrated inside the epidermis by double immunogold labeling and immunoelectron-microscopic examination (46).…”

“…However, epidermal dendritic cell phenotyping, a recently standardized technique based on the¯ow cytometric analysis of epidermal single-cell suspensions from in¯ammatory skin lesions, has the advantage of high sensitivity and speci®city in combination with the potential to analyze individual skin lesions (44, 45). This method is based on the immunophenotype of the two CD1a-positive epidermal cell populations present in in¯ammatory human skin; namely, Langerhans cells and in¯ammatory dendritic epidermal cells (IDEC) (46).…”

“…Beside the Birbeck's granule-containing Langerhans cells, a second CD1a-expressing cell population lacking this Langerhans cell-speci®c ultrastructural hallmark could be demonstrated inside the epidermis by double immunogold labeling and immunoelectron-microscopic examination (46). The immunophenotype and ultrastructure of the latter cell type, the IDEC, have been characterized (45,46), but its ontogenesis and function are still under investigation. Since a hyperstimulatory function of the in vivo mixture of Langerhans cells and IDEC could be demonstrated (87), and both cell types have been shown to express costimulatory molecules on their cell surface (88), a proin¯ammatory function of IDEC may be assumed.…”

The role of antigen presenting cells at distinct anatomic sites: they accelerate and they slow down allergies

“…It is therefore a challenge to understand in which way DC subtypes located at distinct anatomic sites with frequent allergen exposure, such as the skin, the nasal mucosa, the respiratory tree or the mucosa of the intestinal tract can have an impact on mechanisms involved in tolerance induction or effective immunity. monocytes of the peripheral blood into the inflammatory skin lesions (7)(8)(9)(10)(11)(12). A hallmark of both, epidermal LC and IDEC in the skin lesions of AD patients is the elevated expression of the high affinity receptor for immunoglobulin (IgE) (FceRI) ( Table 1) (13)(14)(15)(16)(17).…”

Les cellules dendritiques inflammatoires

“…Dans la peau, on trouve trois populations de cellules dendritiques migratoires : les cellules dendritiques dermiques CD1a + et CD14 + , et les cellules de Langerhans épidermiques [33]. Des cellules dendritiques épidermiques inflammatoires ont été décrites en 1996 dans la peau de patients présentant une dermatite atopique [23]. Ces cellules exprimaient des molécules de surface différentes de celles qu'expriment les cellules dendritiques dermiques et des cellules de Langerhans issues de peau saine.…”